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The Use of Dynamic Pharmacophore in Computer-Aided Hit Discovery: A Case Study

  • Ugo Perricone
  • Marcus Wieder
  • Thomas Seidel
  • Thierry Langer
  • Alessandro Padova
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1824)

Abstract

In recent years pharmacophore modeling has become increasingly popular due to the development of software solutions and improvement in algorithms that allowed researchers to focus on interactions between protein and ligands instead of technical details of the software. At the same time, progress in computer hardware made molecular dynamics (MD) simulations on regular PC hardware possible. MD simulations are usually used, within the virtual screening process, to take into account the flexibility of the target and studying it in more realistic way. In order to do so, it is customary to use simulations before the virtual screening process and then use them for collecting some specific conformation of the target used. Furthermore, some researchers have demonstrated that the use of multiple crystal structures of the same protein can be valuable to better explore the role of the ligand within the binding pocket and then evaluate the most important interactions that are created during the host-guest recognition process. Findings derived from the MD analysis, especially focused on interactions, can be in fact exploited as features for pharmacophore generation or constraints to be used in the molecular docking as integrated steps of the whole virtual screening process. In this chapter, we will present the recent advances in the field pharmacophore modeling combined with the use of MD, a field well explored by our research group in the last 2 years.

Key words

Pharmacophore modeling Molecular dynamics Dynamic pharmacophore Structure-based drug design Virtual screening 

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Ugo Perricone
    • 1
  • Marcus Wieder
    • 2
    • 3
  • Thomas Seidel
    • 2
  • Thierry Langer
    • 2
  • Alessandro Padova
    • 1
  1. 1.Computer-Aided Drug Design Group, Fondazione Ri.MEDPalermoItaly
  2. 2.Faculty of Life Sciences, Department of Pharmaceutical ChemistryUniversity of ViennaViennaAustria
  3. 3.Faculty of Chemistry, Department of Computational Biological ChemistryUniversity of ViennaViennaAustria

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